Harold E. Himwich

A comparison of effects of reserpine and some barbiturates on the electrical activity of cortical and subcortical structures of the brain of rabbits.

Reserpine (Serpasil), an alkaloid from Rauwo[fia serpenha,’ . has been found useful in the management of disturbed psychotic patient^.^. Unlike barbiturates, it renders patients less active without inducing sleep. This action, peculiar to reserpine, has been called a tranquilizing effect. Evidence that this state of quiescence is distinctly different from sedation induced by barbiturates is revealed by the fact that, in monkeys, reserpine does not produce an electroencephalographic picture of sleep.5 I t has been shown that the hypnotic action of barbiturates is related to the depression that these drugs exert upon the brainstem arousal mechanism.6 This fact inspired our work, the aim of which was to investigate further the nature of the tranquilizing effect of reserpine in its relationship with the action of this drug upon the electrical activity of the brain and the function of the mesodiencephalic activating system. Under the unitary denomination “mesodiencephalic activating system” (MDAS), we include, for purposes of description, the reticular formation of the brainstem tegmentum of Moruzzi and Magoun’ and the thalamic diffuse projection system of Jasper.8 Both these structures have the property, when stimulated, of altering, in a diffuse manner, the electrical activity of the cerebral cortex, producing the so-called electrographic alerting or activating or arousal responses. Drugs that produce widespread electrocorticographic changes that consist only of enhancement of the spontaneous sleeping characteristics or, conversely, of those of alertness, act upon the MDAS. Inhibition of the MDAS brings about a dominance of the features of sleep, whereas stimulation of the MDAS causes a predominance of the alert picture. In the experiments reported in this paper, the actions of reserpine, pentobarbital, thiopental, and phenobarbital upon the cerebral electrical activity and upon the MDAS were studied in rabbits. The effects of reserpine and barbiturates will be compared to that of atropine, specific depressant of the MDAS.g Thudickiim Psychiatric Research Laboratory, Galesbwg SIafe Research Hospilal, Galesburg, I l l .

Reserpine, monoamine oxidase inhibitors, and distribution of biogenic amines in monkey brain

Abstract Twenty-one macacus rhesus monkeys were given reserpine, and monoamine oxidase inhibitors (nialamide and isocarboxazid), both singly and in combination, and the levels of serotonin and norepinephrine were determined in various brain regions. The distributional pattern of these amines in monkey brain followed closely that described for other mammals. This primate species resembles rodents, not cats or dogs, in its biochemical response to monoamine oxidase inhibitors inasmuch as nialamide and isocarboxazid increased the brain levels not only of serotonin but also that of norepinephrine. The two inhibitors differed considerably in their interaction with reserpine. The combination of reserpine and isocarboxazid resulted in lower levels of brain amines than when the inhibitor was given alone. The combination of reserpine and nialamide resulted in higher brain serotonin levels than when only nialamide was administered. For this reason it is concluded that, under our experimental conditions, nialamide exerted more than the single action of inhibition of monoamine oxidase.

Amines and schizophrenia

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Indolethylamine-N-methyltransferase in serum samples of schizophrenics and normal controls

Abstract The incidence of N-methyltransferase in blood samples from eleven normal controls, seven acute schizophrenics and eighteen chronic schizophrenics with acute episodes was investigated. The presence of the enzyme was determined by a simple, but highly sensitive, method using two-dimensional thin-layer chromatography and o -phthaladehyde spray reagent. Serotonin (5-HT) and 5-methoxytryptamine (5-OMeT) were used as substrates. The normal samples did not show any bufotenin spots when 5-HT was used as the substrate or 5-methoxy-N:N-dimethyltryptamine (5-OMeDMT) spots with 5-OMeT as the substrate. Of the seven samples from the acute schizophrenics, six showed spots isographic with bufotenin or 5-OMeDMT, and thirteen of the eighteen samples from the chronic schizophrenics were positive for bufotenin or 5-OMeDMT.

Endogenous Metabolic Factor in Schizophrenic Behavior

Exacerbations of schizophrenic behavior are associated with elevations of urinary tryptophan metabolites. Free tryptophan and methionine possibly arising from the breakdown of muscle protein may act like an endogenous metabolic factor which enhances behavioral worsening. Some of the apparently spontaneous activations of psychotic symptoms may be intensified by the endogenous liberation of these two compounds.

Inhibition of indolethylamine-N-methyltransferase by S-Adenosylhomocysteine

Abstract S -Adenosylhomocysteine (SAH) is a potent product inhibitor for indoleamine- N -methyltransferase (INMT) from rabbit lung. The kinetic studies showed that this inhibition was competitive with respect to S -adenosylmethionine (SAM) and noncompetitive with respect to N -methylserotonin (NMS). The K i value of 1.0 × 10−5M indicated that SAH had a higher affinity than SAM or NMS for the enzyme. SAH seems to form a reversible complex with the enzyme.

An Examination of a Possible Cortical Cholinergic Link in the EEG Arousal Reaction

Publisher Summary This chapter presents experiments for possible cortical cholinergic link in the electroencephalogram (EEG) arousal reaction that were performed on 90 adult albino rabbits weighing between 2.5 to 3.0 kg. The topical application of the cholinolytic drugs benactyzine, scopolamine and atropine blocked previously established EEG alerting evoked by eserine or pilocarpine administered intravenously. The cholinolytic drugs also evoked synchronization when alerting was induced by peripheral stimulation as well as after the electrical stimulation of the midbrain. In addition, the cholinolytic drugs were effective in blocking alerting induced by i.v. amphetamine and 5-hydroxytryptophan. Carbocaine as well as pontocaine, and the latter is a far more potent anesthetic than either atropine or benactyzine, failed to interfere with arousal patterns. It is therefore suggested that the ability of the cholinolytic drugs we used to interfere with the EEG alerting reaction is a specific effect and not due to local anesthesia.

Psychotomimetic indole compound in the urine of schizophrenics and mentally defective patients.

BUFOTENIN (Fig. 1), an indole compound first found in the glandular secretion of certain toad species, has been reported to produce psychotic episodes in physically and mentally healthy individuals1. Interest has been focused on this compound in the study of biochemical aspects of schizophrenia because of the possible formation of bufotenin in mammalian tissues from the naturally occurring neurohormone serotonin2,3. A bufotenin-like compound has been reported in the urine of schizophrenic patients4–6. Unfortunately, these findings have not been generally accepted because of some defects in the detection methods employed7,8. Others7,9–15 have failed to confirm the presence of bufotenin in the urine of schizophrenics as well as non-schizophrenic individuals.

Composition of the Milk of the Monkey (M. mulatto)

Summary 1. Monkeys milk tends toward that of the human in composition and differs from cows milk in having a lower percentage of protein and ash and a higher percentage of milk sugar. 2. A modification of cows milk for infant monkey (M. mulatta) feeding is described.

Mescaline, 3,4-Dimethoxyphenylethylamine, and Adrenaline: Sites of Electroencephalographic Arousal

Transections of the brain of rabbit reveal that electroencephalographic arousal produced by injections of adrenaline takes place at the midbrain level, while mescaline and 3,4-dimethoxyphenylethylamine induce such arousal lower in the brainstem, at the medullary level.